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pmid:33540700

A Novel Ferroptosis-Associated Gene Signature to Predict Prognosis in Patients with Uveal Melanoma.

Huan Luo · Chao Ma

Diagnostics (Basel, Switzerland) · 2021 doi:10.3390/diagnostics11020219

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complete

Experiment

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
id
pmid:33540700
kind
science-record
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sha256:4157023261099a3e7655e3ff011f3f8e976c29a98b90c5f206578d20828f1f98
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https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json
created_at
2026-11-01T15:41:24Z
updated_at
2026-11-01T22:03:02Z
generator object · 2 fields
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paper object · 10 fields
state
complete
title
A Novel Ferroptosis-Associated Gene Signature to Predict Prognosis in Patients with Uveal Melanoma.
doi
10.3390/diagnostics11020219
pmid
33540700
authors array · 2 items
[0]
Huan Luo
[1]
Chao Ma
journal
Diagnostics (Basel, Switzerland)
year
2021
abstract
BACKGROUND: Uveal melanoma (UM) is the most common intraocular tumor in adults. Ferroptosis is a newly recognized process of cell death, which is different from other forms of cell death in terms of morphology, biochemistry and genetics, and has played a vital role in cancer biology. The present research aimed to construct a gene signature from ferroptosis-related genes that have the prognostic capacity of UM. METHODS: UM patients from The Cancer Genome Atlas (TCGA) were taken as the training cohort, and GSE22138 from Gene Expression Omnibus (GEO) was treated as the validation cohort. A total of 103 ferroptosis-related genes were retrieved from the GeneCards. We performed Kaplan-Meier and univariate Cox analysis for preliminary screening of ferroptosis-related genes with potential prognostic capacity in the training cohort. These genes were then applied into an overall survival-based LASSO Cox regression model, constructing a gene signature. The discovered gene signature was then evaluated via Kaplan-Meier (KM), Cox, and ROC analyses in both cohorts. The Pearson correlation coefficient examined the correlations between risk score and UM common mutations and autophagy. The analyses of GSEA and immune infiltrating were performed to better study the functional annotation of the gene signature and the character of each kind of immune cell in the tumor microenvironment. RESULTS: A seven-gene signature was found from the training cohort and validated in all cohorts by Kaplan-Meier and Cox regression analyses, revealing its independent prognosis value in UM. Moreover, ROC analysis was conducted, confirming the strong predictive ability that this signature had for UM prognosis. A total of 52.24% (256/490) autophagy-related genes were significantly correlated with risk scores. Analyses of GSEA and immune infiltrating detailed exhibited specific pathways associated with the seven-gene signature, also confirming the crucial role that Mast cells resting played in the prognosis of the seven-gene signature. CONCLUSIONS: In this study, a novel ferroptosis-related seven-gene signature (ALOX12, CD44, MAP1LC3C, STEAP3, HMOX1, ITGA6, and AIFM2/FSP1) was built. It could accurately predict UM prognosis and was related to Mast cells resting, which provides the potential for personalized outcome prediction and the development of new therapies in the UM population.
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The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138.
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sections[26] "Data Availability Statement" paragraph 2
quote
The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138.
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the published estimate and its evidence
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Apply the paper's statistical method to the resolved series and compare the result with the published target.
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The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138.
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The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138.
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Homo sapiens
title
Expression Data from Uveal Melanoma primary tumors.
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Clinical characteristics of patients involved in the study.
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PMC7913108
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11
section_title
3.1. Characteristics of UMs
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80
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4
table object · 8 fields
label
Table 1
caption
Clinical characteristics of patients involved in the study.
rows array · 80 items
[0] array · 3 items
[0]
Characteristics
[1]
Training Cohort (TCGA-UVM, 80 Cases)
[2]
Validation Cohort (GSE22138, 63 Cases)
[1] array · 4 items
[0]
age
[1]
[2]
[3]
[2] array · 4 items
[0]
[1]
<65
[2]
45(56.25%)
[3]
36(57.14%)
[3] array · 4 items
[0]
[1]
≥65
[2]
35(43.75%)
[3]
27(42.86%)
[4] array · 3 items
[0]
gender
[1]
[2]
[5] array · 4 items
[0]
[1]
female
[2]
35(43.75%)
[3]
24(38.1%)
[6] array · 4 items
[0]
[1]
male
[2]
45(56.25%)
[3]
39(61.9%)
[7] array · 3 items
[0]
T classification
[1]
[2]
[8] array · 4 items
[0]
[1]
T1
[2]
0
[3]
NA
[9] array · 4 items
[0]
[1]
T2
[2]
4(5%)
[3]
NA
[10] array · 4 items
[0]
[1]
T3
[2]
36(45%)
[3]
NA
[11] array · 4 items
[0]
[1]
T4
[2]
38(47.5%)
[3]
NA
[12] array · 4 items
[0]
[1]
unknown
[2]
2(2.5%)
[3]
NA
[13] array · 3 items
[0]
M classification
[1]
[2]
[14] array · 4 items
[0]
[1]
M0
[2]
73(91.25%)
[3]
28(44.44%)
[15] array · 4 items
[0]
[1]
M1
[2]
3(3.75%)
[3]
35(55.56%)
[16] array · 4 items
[0]
[1]
unknown
[2]
4(5%)
[3]
0
[17] array · 3 items
[0]
tumor stage
[1]
[2]
[18] array · 4 items
[0]
[1]
stage I
[2]
0
[3]
NA
[19] array · 4 items
[0]
[1]
stage II
[2]
36(45%)
[3]
NA
[20] array · 4 items
[0]
[1]
stage III
[2]
40(50%)
[3]
NA
[21] array · 4 items
[0]
[1]
stage IV
[2]
4(5%)
[3]
NA
[22] array · 3 items
[0]
extrascleral extension
[1]
[2]
[23] array · 4 items
[0]
[1]
yes
[2]
7(8.75%)
[3]
5(7.94%)
[24] array · 4 items
[0]
[1]
no
[2]
68(85%)
[3]
48(76.19%)
[25] array · 4 items
[0]
[1]
unknown
[2]
5(6.25%)
[3]
10(15.87%)
[26] array · 3 items
[0]
tumor diameter, mm
[1]
[2]
[27] array · 4 items
[0]
[1]
<20
[2]
60(75%)
[3]
44(69.84%)
[28] array · 4 items
[0]
[1]
≥20
[2]
19(23.75%)
[3]
9(14.29%)
[29] array · 4 items
[0]
[1]
unknown
[2]
1(1.25%)
[3]
10(15.87%)
[30] array · 3 items
[0]
tumor thickness, mm
[1]
[2]
[31] array · 4 items
[0]
[1]
<10
[2]
29(36.25%)
[3]
10(15.87%)
[32] array · 4 items
[0]
[1]
≥10
[2]
51(63.75%)
[3]
53(84.13%)
[33] array · 3 items
[0]
tumor eye side
[1]
[2]
[34] array · 4 items
[0]
[1]
left
[2]
NA
[3]
33(52.38%)
[35] array · 4 items
[0]
[1]
right
[2]
NA
[3]
30(47.62%)
[36] array · 3 items
[0]
tumor location
[1]
[2]
[37] array · 4 items
[0]
[1]
all over the eye
[2]
NA
[3]
1(1.59%)
[38] array · 4 items
[0]
[1]
anterior to equator
[2]
NA
[3]
3(4.76%)
[39] array · 4 items
[0]
[1]
on equator
[2]
NA
[3]
42(66.67%)
[40] array · 4 items
[0]
[1]
posterior and on equator
[2]
NA
[3]
3(4.76%)
[41] array · 4 items
[0]
[1]
posterior to equator
[2]
NA
[3]
9(14.29%)
[42] array · 4 items
[0]
[1]
unknown
[2]
NA
[3]
5(7.94%)
[43] array · 3 items
[0]
tumor cell type
[1]
[2]
[44] array · 4 items
[0]
[1]
epithelioid
[2]
NA
[3]
21(33.33%)
[45] array · 4 items
[0]
[1]
mixed
[2]
NA
[3]
23(36.51%)
[46] array · 4 items
[0]
[1]
unknown
[2]
NA
[3]
19(30.16%)
[47] array · 3 items
[0]
eye color
[1]
[2]
[48] array · 4 items
[0]
[1]
blue
[2]
9(11.25%)
[3]
NA
[49] array · 4 items
[0]
[1]
brown
[2]
15(18.75%)
[3]
NA
[50] array · 4 items
[0]
[1]
green
[2]
6(7.5%)
[3]
NA
[51] array · 4 items
[0]
[1]
unknown
[2]
50(62.5%)
[3]
NA
[52] array · 3 items
[0]
person neoplasm cancer status
[1]
[2]
[53] array · 4 items
[0]
[1]
with tumor
[2]
9(11.25%)
[3]
NA
[54] array · 4 items
[0]
[1]
tumor free
[2]
56(70%)
[3]
NA
[55] array · 4 items
[0]
[1]
unknown
[2]
15(18.75%)
[3]
NA
[56] array · 3 items
[0]
radiation therapy
[1]
[2]
[57] array · 4 items
[0]
[1]
yes
[2]
3(3.75%)
[3]
NA
[58] array · 4 items
[0]
[1]
no
[2]
63(78.75%)
[3]
NA
[59] array · 4 items
[0]
[1]
unknown
[2]
14(17.5%)
[3]
NA
[60] array · 3 items
[0]
ethnicity
[1]
[2]
[61] array · 4 items
[0]
[1]
hispanic or latino
[2]
1(1.25%)
[3]
NA
[62] array · 4 items
[0]
[1]
not hispanic or latino
[2]
52(65%)
[3]
NA
[63] array · 4 items
[0]
[1]
unknown
[2]
27(33.75%)
[3]
NA
[64] array · 3 items
[0]
tissue or organ of origin diagnosis
[1]
[2]
[65] array · 4 items
[0]
[1]
choroid
[2]
67(83.75%)
[3]
NA
[66] array · 4 items
[0]
[1]
ciliary body
[2]
5(6.25%)
[3]
NA
[67] array · 4 items
[0]
[1]
overlapping lesion of eye and adnexa
[2]
8(10%)
[3]
NA
[68] array · 3 items
[0]
retinal detachment
[1]
[2]
[69] array · 4 items
[0]
[1]
yes
[2]
NA
[3]
36(57.14%)
[70] array · 4 items
[0]
[1]
no
[2]
NA
[3]
22(34.92%)
[71] array · 4 items
[0]
[1]
unknown
[2]
NA
[3]
5(7.94%)
[72] array · 3 items
[0]
mitotic count
[1]
[2]
[73] array · 4 items
[0]
[1]
<20
[2]
42(52.5%)
[3]
NA
[74] array · 4 items
[0]
[1]
≥20
[2]
11(13.75%)
[3]
NA
[75] array · 4 items
[0]
[1]
unknown
[2]
27(33.75%)
[3]
NA
[76] array · 3 items
[0]
chromosome 3 status
[1]
[2]
[77] array · 4 items
[0]
[1]
disomy
[2]
NA
[3]
18(28.57%)
[78] array · 4 items
[0]
[1]
monosomy
[2]
NA
[3]
37(58.73%)
[79] array · 4 items
[0]
[1]
unknown
[2]
NA
[3]
8(12.7%)
locator
section[11]/table-wrap[1]#diagnostics-11-00219-t001
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22 ferroptosis-related potential prognostic genes generated from the training cohort.
structure object · 5 fields
pmcid
PMC7913108
section_index
12
section_title
3.2. Identification of Prognostic Ferroptosis-Related Gene Signature
row_count
24
column_count
9
table object · 8 fields
label
Table 2
caption
22 ferroptosis-related potential prognostic genes generated from the training cohort.
rows array · 24 items
[0] array · 6 items
[0]
Gene Symbol
[1]
Description
[2]
Category
[3]
Genomic Location
[4]
Kaplan–Meier Analysis (p-Value)
[5]
Univariate Cox Regression Analysis
[1] array · 4 items
[0]
HR
[1]
HR_95L
[2]
HR_95H
[3]
p-Value
[2] array · 9 items
[0]
VDAC1
[1]
Voltage Dependent Anion Channel 1
[2]
Protein Coding
[3]
chr5
[4]
7.12 × 10−6
[5]
5.291343594
[6]
1.781142996
[7]
15.71929771
[8]
2.71 × 10−3
[3] array · 9 items
[0]
STEAP3
[1]
STEAP3 Metalloreductase
[2]
Protein Coding
[3]
chr2
[4]
3.19 × 10−3
[5]
4.206162616
[6]
2.092921898
[7]
8.453160136
[8]
5.49 × 10−5
[4] array · 9 items
[0]
SLC39A8
[1]
Solute Carrier Family 39 Member 8
[2]
Protein Coding
[3]
chr4
[4]
3.77 × 10−2
[5]
3.869852511
[6]
1.326333156
[7]
11.29109861
[8]
1.33 × 10−2
[5] array · 9 items
[0]
SLC11A2
[1]
Solute Carrier Family 11 Member 2
[2]
Protein Coding
[3]
chr12
[4]
4.76 × 10−3
[5]
3.094601274
[6]
1.570769273
[7]
6.096730571
[8]
1.09 × 10−3
[6] array · 9 items
[0]
PEBP1
[1]
Phosphatidylethanolamine Binding Protein 1
[2]
Protein Coding
[3]
chr12
[4]
4.86 × 10−2
[5]
0.234529606
[6]
0.075635069
[7]
0.727230595
[8]
1.20 × 10−2
[7] array · 9 items
[0]
MAPK1
[1]
Mitogen−Activated Protein Kinase 1
[2]
Protein Coding
[3]
chr22
[4]
9.03 × 10−3
[5]
2.895607401
[6]
1.163501743
[7]
7.206299663
[8]
2.23 × 10−2
[8] array · 9 items
[0]
MAP1LC3C
[1]
Microtubule Associated Protein 1 Light Chain 3 Gamma
[2]
Protein Coding
[3]
chr1
[4]
1.31 × 10−2
[5]
0.459748503
[6]
0.271733125
[7]
0.777853955
[8]
3.78 × 10−3
[9] array · 9 items
[0]
LINC00472
[1]
Long Intergenic Non-Protein Coding RNA 472
[2]
RNA Gene
[3]
chr6
[4]
6.36 × 10−3
[5]
0.043258919
[6]
0.003322917
[7]
0.563160037
[8]
1.65 × 10−2
[10] array · 9 items
[0]
ITGA6
[1]
Integrin Subunit Alpha 6
[2]
Protein Coding
[3]
chr2
[4]
1.13 × 10−3
[5]
4.613594536
[6]
2.148024539
[7]
9.909223176
[8]
8.85 × 10−5
[11] array · 9 items
[0]
HSPA5
[1]
Heat Shock Protein Family A (Hsp70) Member 5
[2]
Protein Coding
[3]
chr9
[4]
8.91 × 10−3
[5]
2.25326069
[6]
1.228917946
[7]
4.131426149
[8]
8.63 × 10−3
[12] array · 9 items
[0]
HMOX1
[1]
Heme Oxygenase 1
[2]
Protein Coding
[3]
chr22
[4]
2.19 × 10−3
[5]
2.334473768
[6]
1.59857086
[7]
3.409149952
[8]
1.14 × 10−5
[13] array · 9 items
[0]
GSS
[1]
Glutathione Synthetase
[2]
Protein Coding
[3]
chr20
[4]
3.31 × 10−3
[5]
3.851728269
[6]
1.85357871
[7]
8.003874117
[8]
3.02 × 10−4
[14] array · 9 items
[0]
FTH1
[1]
Ferritin Heavy Chain 1
[2]
Protein Coding
[3]
chr11
[4]
4.64 × 10− 3
[5]
4.040699109
[6]
1.10619952
[7]
14.75976891
[8]
3.46 × 10−2
[15] array · 9 items
[0]
CD44
[1]
CD44 Molecule (Indian Blood Group)
[2]
Protein Coding
[3]
chr11
[4]
6.66 × 10− 3
[5]
0.304760194
[6]
0.142947413
[7]
0.649740862
[8]
2.10 × 10−3
[16] array · 9 items
[0]
CASP8
[1]
Caspase 8
[2]
Protein Coding
[3]
chr2
[4]
3.91 × 10−2
[5]
2.604965341
[6]
1.209052632
[7]
5.612530215
[8]
1.45 × 10−2
[17] array · 9 items
[0]
BAP1
[1]
BRCA1 Associated Protein 1
[2]
Protein Coding
[3]
chr3
[4]
1.40 × 10−6
[5]
0.561778701
[6]
0.412394493
[7]
0.765275275
[8]
2.56 × 10−4
[18] array · 9 items
[0]
AURKA
[1]
Aurora Kinase A
[2]
Protein Coding
[3]
chr20
[4]
2.54 × 10−2
[5]
3.390492663
[6]
1.565174215
[7]
7.344511806
[8]
1.96 × 10−3
[19] array · 9 items
[0]
ANO6
[1]
Anoctamin 6
[2]
Protein Coding
[3]
chr12
[4]
2.56 × 10−2
[5]
2.263254914
[6]
1.292723147
[7]
3.962428319
[8]
4.26 × 10−3
[20] array · 9 items
[0]
ALOX12
[1]
Arachidonate 12-Lipoxygenase, 12S Type
[2]
Protein Coding
[3]
chr17
[4]
1.48 × 10−3
[5]
0.022909689
[6]
0.002539428
[7]
0.20668188
[8]
7.66 × 10−4
[21] array · 9 items
[0]
AIFM2/FSP1
[1]
Apoptosis Inducing Factor Mitochondria Associated 2
[2]
Protein Coding
[3]
chr10
[4]
6.03 × 10−6
[5]
6.104896507
[6]
2.780109603
[7]
13.40586045
[8]
6.55 × 10−6
[22] array · 9 items
[0]
ACSL6
[1]
Acyl-CoA Synthetase Long Chain Family Member 6
[2]
Protein Coding
[3]
chr5
[4]
4.56 × 10−4
[5]
2.283441779
[6]
1.099533069
[7]
4.742109633
[8]
2.68 × 10−2
[23] array · 9 items
[0]
ACSL1
[1]
Acyl-CoA Synthetase Long Chain Family Member 1
[2]
Protein Coding
[3]
chr4
[4]
6.64 × 10−3
[5]
1.873686292
[6]
1.236619189
[7]
2.838950221
[8]
3.06 × 10−3
locator
section[12]/table-wrap[1]#diagnostics-11-00219-t002
[4] object · 16 fields
id
asset:table:pmid:33540700:3
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:58c27e8d0165e8f86a9b747fd69d80eaba41c2b48e51986235ea562936048c61
bytes
928
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[12]/table-wrap[2]#diagnostics-11-00219-t003
version
null
note
7 ferroptosis-related prognostic genes obtained from LASSO Cox regression model.
structure object · 5 fields
pmcid
PMC7913108
section_index
12
section_title
3.2. Identification of Prognostic Ferroptosis-Related Gene Signature
row_count
8
column_count
4
table object · 8 fields
label
Table 3
caption
7 ferroptosis-related prognostic genes obtained from LASSO Cox regression model.
rows array · 8 items
[0] array · 4 items
[0]
Gene Symbol
[1]
Description
[2]
Role
[3]
Risk Coefficient
[1] array · 4 items
[0]
STEAP3
[1]
STEAP3 Metalloreductase
[2]
Marker [26]
[3]
0.055060532
[2] array · 4 items
[0]
MAP1LC3C
[1]
Microtubule Associated Protein 1 Light Chain 3 Gamma
[2]
Driver [27]
[3]
−0.202884346
[3] array · 4 items
[0]
ITGA6
[1]
Integrin Subunit Alpha 6
[2]
Suppressor [28]
[3]
0.34461317
[4] array · 4 items
[0]
HMOX1
[1]
Heme Oxygenase 1
[2]
Driver [29,30,31,32], Suppressor [33,34], Marker [35,36]
[3]
0.125266141
[5] array · 4 items
[0]
CD44
[1]
CD44 Molecule (Indian Blood Group)
[2]
Suppressor [37]
[3]
−0.316011897
[6] array · 4 items
[0]
ALOX12
[1]
Arachidonate 12-Lipoxygenase, 12S Type
[2]
Driver [38,39,40], Marker [41]
[3]
−1.311120914
[7] array · 4 items
[0]
AIFM2/FSP1
[1]
Apoptosis Inducing Factor Mitochondria Associated 2
[2]
Suppressor [42,43]
[3]
0.710789029
locator
section[12]/table-wrap[2]#diagnostics-11-00219-t003
[5] object · 16 fields
id
asset:table:pmid:33540700:4
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:b9d6a1eb3e5b07fea8c9fdd5e38c27d5f3dac16cc113425a84f0e0312bd79e3e
bytes
5193
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[13]/table-wrap[1]#diagnostics-11-00219-t004
version
null
note
Univariate analysis and multivariate analysis of the correlation of gene-signature risk score with outcomes among uveal melanoma patients in two cohorts.
structure object · 5 fields
pmcid
PMC7913108
section_index
13
section_title
3.3. The Prognostic Capacity of the Seven-Gene Signature
row_count
46
column_count
9
table object · 8 fields
label
Table 4
caption
Univariate analysis and multivariate analysis of the correlation of gene-signature risk score with outcomes among uveal melanoma patients in two cohorts.
rows array · 46 items
[0] array · 3 items
[0]
Variable
[1]
Univariate Cox Analysis
[2]
Multivariate Cox Analysis
[1] array · 8 items
[0]
Coef
[1]
HR (95% CI)
[2]
z
[3]
p-Value
[4]
Coef
[5]
HR (95% CI)
[6]
z
[7]
p-Value
[2] array · 9 items
[0]
TCGA-UVM (overall survival) *
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[3] array · 9 items
[0]
age
[1]
0.0447
[2]
1.05 (1.01–1.09)
[3]
2.35
[4]
0.0186
[5]
0.101
[6]
1.11 (0.976–1.25)
[7]
1.57
[8]
0.115
[4] array · 9 items
[0]
gender (male vs. female)
[1]
0.433
[2]
1.54 (0.651–3.65)
[3]
0.984
[4]
0.325
[5]
[6]
[7]
[8]
[5] array · 9 items
[0]
tumor stage (stage III vs. stage II)
[1]
0.336
[2]
1.4 (0.556–3.52)
[3]
0.713
[4]
0.476
[5]
−3.06
[6]
0.047 (0.00199–1.11)
[7]
−1.9
[8]
0.0579
[6] array · 9 items
[0]
tumor stage (stage IV vs. stage II)
[1]
4.37
[2]
79.3 (7.55–834)
[3]
3.64
[4]
0.000269
[5]
NA
[6]
NA
[7]
NA
[8]
NA
[7] array · 9 items
[0]
extrascleral extension (yes vs. no)
[1]
1.54
[2]
4.64 (1.5–14.4)
[3]
2.66
[4]
0.00774
[5]
−4.25
[6]
0.0142 (3.98× 10−13–5.1× 10 8)
[7]
−0.343
[8]
0.732
[8] array · 9 items
[0]
tumor diameter
[1]
0.155
[2]
1.17 (1.01–1.35)
[3]
2.12
[4]
0.0344
[5]
0.723
[6]
2.06 (1.11–3.83)
[7]
2.29
[8]
0.0221
[9] array · 9 items
[0]
tumor thickness
[1]
0.111
[2]
1.12 (0.949–1.32)
[3]
1.33
[4]
0.183
[5]
[6]
[7]
[8]
[10] array · 9 items
[0]
radiation therapy (yes vs. no)
[1]
1.68
[2]
5.35 (1.09–26.3)
[3]
2.07
[4]
0.0389
[5]
7.79
[6]
2410 (4.34 × 10−8–1.33 × 10 14)
[7]
0.617
[8]
0.537
[11] array · 9 items
[0]
ethnicity (hispanic or latino vs. not hispanic or latino)
[1]
−16
[2]
1.09 × 10−7 (0-Inf)
[3]
−0.00205
[4]
0.998
[5]
[6]
[7]
[8]
[12] array · 9 items
[0]
tissue or organ of origin diagnosis (choroid vs. not choroid)
[1]
−0.286
[2]
0.751 (0.254–2.22)
[3]
−0.517
[4]
0.605
[5]
[6]
[7]
[8]
[13] array · 9 items
[0]
mitotic count
[1]
−0.0119
[2]
0.988 (0.931–1.05)
[3]
−0.394
[4]
0.693
[5]
[6]
[7]
[8]
[14] array · 9 items
[0]
chromosome 3 copy number
[1]
−1.86
[2]
0.156 (0.0574–0.422)
[3]
−3.65
[4]
0.00026
[5]
2.76
[6]
15.9 (0.894–281)
[7]
1.88
[8]
0.0597
[15] array · 9 items
[0]
chromosome 6p copy number
[1]
−1.06
[2]
0.348 (0.176–0.687)
[3]
−3.04
[4]
0.00237
[5]
−0.874
[6]
0.417 (0.0559–3.11)
[7]
−0.852
[8]
0.394
[16] array · 9 items
[0]
chromosome 8q copy number
[1]
0.516
[2]
1.67 (1.27–2.2)
[3]
3.68
[4]
0.000235
[5]
−0.88
[6]
0.415 (0.126–1.37)
[7]
−1.44
[8]
0.149
[17] array · 9 items
[0]
risk score
[1]
1.65
[2]
5.22 (2.59–10.5)
[3]
4.61
[4]
3.99 × 10−6
[5]
4.23
[6]
68.6 (3.36–1400)
[7]
2.75
[8]
0.00598
[18] array · 9 items
[0]
TCGA-UVM (progression-free survival) #
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[19] array · 9 items
[0]
age
[1]
0.0271
[2]
1.03 (0.996–1.06)
[3]
1.7
[4]
0.0886
[5]
[6]
[7]
[8]
[20] array · 9 items
[0]
gender (male vs. female)
[1]
−0.139
[2]
0.87 (0.422–1.8)
[3]
−0.376
[4]
0.707
[5]
[6]
[7]
[8]
[21] array · 9 items
[0]
tumor stage (stage III vs. stage II)
[1]
0.381
[2]
1.46 (0.665–3.22)
[3]
0.946
[4]
0.344
[5]
−0.959
[6]
0.383 (0.094–1.56)
[7]
−1.34
[8]
0.181
[22] array · 9 items
[0]
tumor stage (stage IV vs. stage II)
[1]
3.31
[2]
27.4 (5.06–149)
[3]
3.84
[4]
0.000124
[5]
2.87
[6]
17.6 (0.677–455)
[7]
1.73
[8]
0.0845
[23] array · 9 items
[0]
extrascleral extension (yes vs. no)
[1]
1.45
[2]
4.26 (1.57–11.5)
[3]
2.85
[4]
0.0044
[5]
−0.682
[6]
0.506 (0.00917–27.9)
[7]
−0.333
[8]
0.739
[24] array · 9 items
[0]
tumor diameter
[1]
0.113
[2]
1.12 (0.999–1.25)
[3]
1.94
[4]
0.0527
[5]
[6]
[7]
[8]
[25] array · 9 items
[0]
tumor thickness
[1]
0.00859
[2]
1.01 (0.875–1.16)
[3]
0.119
[4]
0.905
[5]
[6]
[7]
[8]
[26] array · 9 items
[0]
radiation therapy (yes vs. no)
[1]
0.0846
[2]
1.09 (0.142–8.33)
[3]
0.0814
[4]
0.935
[5]
[6]
[7]
[8]
[27] array · 9 items
[0]
ethnicity (hispanic or latino vs. not hispanic or latino)
[1]
−17
[2]
3.98 × 10−8 (0-Inf)
[3]
−0.00217
[4]
0.998
[5]
[6]
[7]
[8]
[28] array · 9 items
[0]
tissue or organ of origin diagnosis (choroid vs. not choroid)
[1]
0.0872
[2]
1.09 (0.377–3.16)
[3]
0.161
[4]
0.872
[5]
[6]
[7]
[8]
[29] array · 9 items
[0]
mitotic count
[1]
0.0545
[2]
1.06 (1.01–1.1)
[3]
2.64
[4]
0.00829
[5]
0.0575
[6]
1.06 (0.976–1.15)
[7]
1.37
[8]
0.17
[30] array · 9 items
[0]
chromosome 3 copy number
[1]
−1.86
[2]
0.156 (0.0631–0.386)
[3]
−4.02
[4]
5.88 × 10−5
[5]
−1.3
[6]
0.272 (0.0293–2.52)
[7]
−1.15
[8]
0.252
[31] array · 9 items
[0]
chromosome 6p copy number
[1]
−0.628
[2]
0.534 (0.321–0.888)
[3]
−2.42
[4]
0.0155
[5]
0.709
[6]
2.03 (0.611–6.75)
[7]
1.16
[8]
0.247
[32] array · 9 items
[0]
chromosome 8q copy number
[1]
0.521
[2]
1.68 (1.31–2.16)
[3]
4.08
[4]
4.56 × 10−5
[5]
0.146
[6]
1.16 (0.546–2.45)
[7]
0.381
[8]
0.703
[33] array · 9 items
[0]
risk score
[1]
0.933
[2]
2.54 (1.65–3.91)
[3]
4.25
[4]
2.13 × 10−5
[5]
0.703
[6]
2.02 (0.486–8.39)
[7]
0.967
[8]
0.0334
[34] array · 9 items
[0]
GSE22138 (metastasis-free survival) &
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[35] array · 9 items
[0]
age
[1]
0.0213
[2]
1.02 (0.995–1.05)
[3]
1.59
[4]
0.113
[5]
[6]
[7]
[8]
[36] array · 9 items
[0]
gender (male vs. female)
[1]
0.353
[2]
1.42 (0.714–2.84)
[3]
1
[4]
0.316
[5]
[6]
[7]
[8]
[37] array · 9 items
[0]
tumor eye side (left vs. right)
[1]
−0.193
[2]
0.824 (0.424–1.6)
[3]
−0.57
[4]
0.569
[5]
[6]
[7]
[8]
[38] array · 9 items
[0]
tumor location (on equator vs. others)
[1]
−0.325
[2]
0.723 (0.357–1.46)
[3]
−0.903
[4]
0.366
[5]
[6]
[7]
[8]
[39] array · 9 items
[0]
tumor diameter
[1]
−0.0165
[2]
0.984 (0.893–1.08)
[3]
−0.336
[4]
0.737
[5]
[6]
[7]
[8]
[40] array · 9 items
[0]
tumor thickness
[1]
0.116
[2]
1.12 (0.951–1.33)
[3]
1.37
[4]
0.171
[5]
[6]
[7]
[8]
[41] array · 9 items
[0]
tumor cell type (epithelioid vs. mixed)
[1]
0.753
[2]
2.12 (0.954–4.72)
[3]
1.85
[4]
0.0649
[5]
[6]
[7]
[8]
[42] array · 9 items
[0]
retinal detachment (yes vs. no)
[1]
1.06
[2]
2.87 (1.24–6.68)
[3]
2.45
[4]
0.0142
[5]
0.857
[6]
2.36 (0.981–5.66)
[7]
1.92
[8]
0.0553
[43] array · 9 items
[0]
extrascleral extension (yes vs. no)
[1]
0.563
[2]
1.76 (0.668–4.62)
[3]
1.14
[4]
0.253
[5]
[6]
[7]
[8]
[44] array · 9 items
[0]
chromosome 3 status (monosomy vs. disomy)
[1]
1.67
[2]
5.29 (1.82–15.3)
[3]
3.07
[4]
0.00217
[5]
1.24
[6]
3.45 (1.04–11.5)
[7]
2.02
[8]
0.0435
[45] array · 9 items
[0]
risk score
[1]
0.646
[2]
1.91 (1.31–2.78)
[3]
3.37
[4]
0.000745
[5]
0.523
[6]
1.69 (1.03–2.77)
[7]
2.07
[8]
0.0388
locator
section[13]/table-wrap[1]#diagnostics-11-00219-t004
gaps array · 2 items
[0]
asset:data:geo:GSE22138 not downloaded
[1]
asset:data:geo:GSE22138 licence not read
analysis object · 4 fields
state
complete
methods array · 4 items
[0] object · 10 fields
id
method-1
family
survival_analysis
specific
kaplan_meier
label
Survival analysis
dsl_operations array · 1 item
[0]
survival_km
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.7
band
medium
quote
Kaplan-Meier
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
dsl_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.7
band
medium
quote
Cox regression
[2] object · 10 fields
id
method-3
family
correlation_analysis
specific
pearson
label
Correlation analysis
dsl_operations array · 1 item
[0]
pearson_r
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
paired_numeric_columns
evidence object · 3 fields
score
0.7
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medium
quote
Pearson correlation
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id
method-4
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diagnostic_evaluation
specific
roc
label
Diagnostic test evaluation
dsl_operations array · 6 items
[0]
confusion_counts
[1]
roc_curve
[2]
sensitivity_specificity
[3]
solve_confusion_matrix
[4]
classification_metrics
[5]
published_precision_envelope
missing_operations array · 0 items
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data_shapes array · 1 item
[0]
reference_standard_and_test
evidence object · 3 fields
score
0.7
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medium
quote
ROC analysis
targets array · 0 items
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
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Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
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survival_analysis
[3]
statistical_regression
[4]
pca
[5]
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[6]
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[7]
differential_expression
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gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
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nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
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true
required_operations array · 1 item
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survival_km
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
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true
accessions array · 1 item
[0]
GSE22138
resolved_accessions array · 1 item
[0]
GSE22138
statements array · 1 item
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The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138.
basis
The paper names GSE22138 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 1 item
[0]
survival_km
assets array · 6 items
[0]
source:pmid:33540700
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data:geo:GSE22138
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asset:table:pmid:33540700:1
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asset:table:pmid:33540700:2
[4]
asset:table:pmid:33540700:3
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asset:table:pmid:33540700:4
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
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readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
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data:geo:GSE22138
gaps array · 0 items
review object · 5 fields
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partial
machine_critique object · 5 fields
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extraction_review
reader object · 5 fields
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MiniMax-M3.1-Flash
provider
minimax
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minimax
read_at
2026-10-31T19:23:57Z
independence
single_reader
evidence_check object · 2 fields
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absent
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verbatim
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3
usage object · 3 fields
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50138
completion_tokens
1491
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784
stages array · 1 item
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extraction
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null
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gaps array · 1 item
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provenance object · 7 fields
entities array · 3 items
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pmid:33540700
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paper
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pmid:33540700
[1] object · 3 fields
id
source:pmid:33540700
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manuscript
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PMID 33540700 full text
[2] object · 3 fields
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data:geo:GSE22138
type
dataset
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GEO GSE22138
activities array · 3 items
[0] object · 4 fields
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paper
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pmid:33540700
[1] object · 3 fields
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source:pmid:33540700
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manuscript
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PMID 33540700 full text
[2] object · 3 fields
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data:geo:GSE22138
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dataset
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GEO GSE22138
agent
agent:corpus-assay-engine
[1] object · 4 fields
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activity-read-33540700
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extraction
used array · 1 item
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source:pmid:33540700
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE22138
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accession_resolution
used array · 1 item
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data:geo:GSE22138
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
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agent:corpus-assay-engine
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Corpus assay engine
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agent:minimax-reader
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software
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MiniMax literature reader
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dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
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lineage object · 4 fields
parent_id
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sha256:f8b66e2f0fe087d2be08c948190e97c44b6ce4e093b6ce49ef9d0c87e0190014
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null
gaps array · 6 items
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asset:data:geo:GSE22138 licence not read
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asset:data:geo:GSE22138 not downloaded
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[3]
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[4]
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assays array · 1 item
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f2132e96ae6c7a4e
evidence array · 1 item
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33540700", "kind": "science-record", "revision": 7, "content_hash": "sha256:4157023261099a3e7655e3ff011f3f8e976c29a98b90c5f206578d20828f1f98", "created_at": "2026-11-01T15:41:24Z", "updated_at": "2026-11-01T22:03:02Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A Novel Ferroptosis-Associated Gene Signature to Predict Prognosis in Patients with Uveal Melanoma.", "doi": "10.3390/diagnostics11020219", "pmid": "33540700", "authors": ["Huan Luo", "Chao Ma"], "journal": "Diagnostics (Basel, Switzerland)", "year": 2021, "abstract": "BACKGROUND: Uveal melanoma (UM) is the most common intraocular tumor in adults. Ferroptosis is a newly recognized process of cell death, which is different from other forms of cell death in terms of morphology, biochemistry and genetics, and has played a vital role in cancer biology. The present research aimed to construct a gene signature from ferroptosis-related genes that have the prognostic capacity of UM.\nMETHODS: UM patients from The Cancer Genome Atlas (TCGA) were taken as the training cohort, and GSE22138 from Gene Expression Omnibus (GEO) was treated as the validation cohort. A total of 103 ferroptosis-related genes were retrieved from the GeneCards. We performed Kaplan-Meier and univariate Cox analysis for preliminary screening of ferroptosis-related genes with potential prognostic capacity in the training cohort. These genes were then applied into an overall survival-based LASSO Cox regression model, constructing a gene signature. The discovered gene signature was then evaluated via Kaplan-Meier (KM), Cox, and ROC analyses in both cohorts. The Pearson correlation coefficient examined the correlations between risk score and UM common mutations and autophagy. The analyses of GSEA and immune infiltrating were performed to better study the functional annotation of the gene signature and the character of each kind of immune cell in the tumor microenvironment.\nRESULTS: A seven-gene signature was found from the training cohort and validated in all cohorts by Kaplan-Meier and Cox regression analyses, revealing its independent prognosis value in UM. Moreover, ROC analysis was conducted, confirming the strong predictive ability that this signature had for UM prognosis. A total of 52.24% (256/490) autophagy-related genes were significantly correlated with risk scores. Analyses of GSEA and immune infiltrating detailed exhibited specific pathways associated with the seven-gene signature, also confirming the crucial role that Mast cells resting played in the prognosis of the seven-gene signature.\nCONCLUSIONS: In this study, a novel ferroptosis-related seven-gene signature (ALOX12, CD44, MAP1LC3C, STEAP3, HMOX1, ITGA6, and AIFM2/FSP1) was built. It could accurately predict UM prognosis and was related to Mast cells resting, which provides the potential for personalized outcome prediction and the development of new therapies in the UM population.", "claims": [{"id": "claim-data-access", "statement": "The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33540700", "locator": "sections[26] \"Data Availability Statement\" paragraph 2", "quote": "The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33540700"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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The Prognostic Capacity of the Seven-Gene Signature", "row_count": 46, "column_count": 9}, "table": {"label": "Table 4", "caption": "Univariate analysis and multivariate analysis of the correlation of gene-signature risk score with outcomes among uveal melanoma patients in two cohorts.", "rows": [["Variable", "Univariate Cox Analysis", "Multivariate Cox Analysis"], ["Coef", "HR (95% CI)", "z", "p-Value", "Coef", "HR (95% CI)", "z", "p-Value"], ["TCGA-UVM (overall survival) *", "", "", "", "", "", "", "", ""], ["age", "0.0447", "1.05 (1.01–1.09)", "2.35", "0.0186", "0.101", "1.11 (0.976–1.25)", "1.57", "0.115"], ["gender (male vs. female)", "0.433", "1.54 (0.651–3.65)", "0.984", "0.325", "", "", "", ""], ["tumor stage (stage III vs. stage II)", "0.336", "1.4 (0.556–3.52)", "0.713", "0.476", "−3.06", "0.047 (0.00199–1.11)", "−1.9", "0.0579"], ["tumor stage (stage IV vs. stage II)", "4.37", "79.3 (7.55–834)", "3.64", "0.000269", "NA", "NA", "NA", "NA"], ["extrascleral extension (yes vs. no)", "1.54", "4.64 (1.5–14.4)", "2.66", "0.00774", "−4.25", "0.0142 (3.98× 10−13–5.1× 10 8)", "−0.343", "0.732"], ["tumor diameter", "0.155", "1.17 (1.01–1.35)", "2.12", "0.0344", "0.723", "2.06 (1.11–3.83)", "2.29", "0.0221"], ["tumor thickness", "0.111", "1.12 (0.949–1.32)", "1.33", "0.183", "", "", "", ""], ["radiation therapy (yes vs. no)", "1.68", "5.35 (1.09–26.3)", "2.07", "0.0389", "7.79", "2410 (4.34 × 10−8–1.33 × 10 14)", "0.617", "0.537"], ["ethnicity (hispanic or latino vs. not hispanic or latino)", "−16", "1.09 × 10−7 (0-Inf)", "−0.00205", "0.998", "", "", "", ""], ["tissue or organ of origin diagnosis (choroid vs. not choroid)", "−0.286", "0.751 (0.254–2.22)", "−0.517", "0.605", "", "", "", ""], ["mitotic count", "−0.0119", "0.988 (0.931–1.05)", "−0.394", "0.693", "", "", "", ""], ["chromosome 3 copy number", "−1.86", "0.156 (0.0574–0.422)", "−3.65", "0.00026", "2.76", "15.9 (0.894–281)", "1.88", "0.0597"], ["chromosome 6p copy number", "−1.06", "0.348 (0.176–0.687)", 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"capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE22138"], "resolved_accessions": ["GSE22138"], "statements": ["The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138."], "basis": "The paper names GSE22138 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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